{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T07:59:20Z","timestamp":1781078360036,"version":"3.54.1"},"reference-count":21,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Objectives: To investigate the clinicopathologic characteristics and molecular biomarkers of atypical vasoproliferative retinal tumor (VPRT) with hemangioblastoma-like histopathologic features and concomitant von Willebrand factor (VWF) abnormalities. Methods: A 48-year-old woman undergoing phacoemulsification and 25-gauge pars plana vitrectomy with tumor resection was evaluated. Histopathological findings and immunohistochemical study of the resected tumor were performed using CD34, \u03b1-smooth muscle actin (\u03b1SMA), and glial fibrillary acidic protein (GFAP) markers. Preoperative plasma and intraoperative vitreous fluid VWF antigen levels, as well as ristocetin cofactor activity, were quantified using latex immunoturbidimetry. Results: Ultra-widefield imaging and angiography demonstrated a peripheral retinal tumor with intense vascular leakage and surrounding capillary nonperfusion. Histopathology showed hyalinized vascular components supportive of VPRT, along with abundant CD34\/\u03b1-SMA-positive microvessels and scant GFAP-positive glial cells. Notably, numerous foamy vacuolated poorly differentiated cells suggested mixed hemangioblastoma-like features. Preoperative plasma VWF antigen (182.6%) and ristocetin cofactor activity (147.7%) were elevated, and vitreous VWF antigen was successfully detected at a low but distinct level (7.7%).and suggests that VWF abnormalities in the plasma and vitreous may reflect endothelial activation and\/or blood\u2013retinal barrier disruption in a subset of vascularized retinal tumors. Conclusions: Our findings demonstrate that VPRT may exhibit mixed clinicopathologic features, including hemangioblastoma-like components, which underscores the necessity of immunohistochemical assessment for definitive diagnosis. Furthermore, the quantification of VWF abnormalities in the plasma and vitreous suggests that VWF serves as a potential biomarker reflecting endothelial activation and\/or blood\u2013retinal barrier disruption in vascularized retinal tumors.<\/jats:p>","DOI":"10.3390\/jcm15124440","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T16:25:16Z","timestamp":1780935916000},"page":"4440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Vasoproliferative Retinal Tumor with Hemangioblastoma-like Features: Evaluation with von Wilebrand Factor"],"prefix":"10.3390","volume":"15","author":[{"given":"Daiki","family":"Kuraoka","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Nara Medical University, Kashihara 8348521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7607-0975","authenticated-orcid":false,"given":"Hiromasa","family":"Hirai","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Nara Medical University, Kashihara 8348521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Morimoto","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Nara Medical University, Kashihara 8348521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0523-7931","authenticated-orcid":false,"given":"Kazuya","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion Medicine, Nara Medical University, Kashihara 8348521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1462-7341","authenticated-orcid":false,"given":"Akihiko","family":"Yoshizawa","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology, Nara Medical University, Kashihara 8348521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3426-1674","authenticated-orcid":false,"given":"Satoru","family":"Kase","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Nara Medical University, Kashihara 8348521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1136\/bjo.84.10.1162","article-title":"Vasoproliferative tumours of the retina","volume":"84","author":"Heimann","year":"2000","journal-title":"Br. J. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1136\/bjo.2005.086066","article-title":"Vasoproliferative retinal tumour","volume":"90","author":"Damato","year":"2006","journal-title":"Br. J. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1001\/2013.jamaophthalmol.524","article-title":"Retinal vasoproliferative tumors: Coparative clinical features of primary vs secondary tumors in 334 cases","volume":"131","author":"Shields","year":"2013","journal-title":"JAMA Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.ajo.2012.09.002","article-title":"Reactive retinal astrocytic tumors (so-called vasoproliferative tumors): Histopathologic, immunohistochemical, and genetic studies of four cases","volume":"155","author":"Perry","year":"2013","journal-title":"Am. J. Ophthalmol."},{"key":"ref_5","first-page":"3067","article-title":"Retinal hemangioblastoma in von Hippel-Lindau disease: A clinical and molecular study","volume":"43","author":"Dollfus","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s10384-009-0699-y","article-title":"Expression of inhibin \u03b1 by stromal cells of retinal angiomas excised from a patient with von Hippel-Lindau disease","volume":"53","author":"Miyazawa","year":"2009","journal-title":"Jpn. J. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0046-8177(82)80133-0","article-title":"Hemangioblastomas: Histogenesis of the stromal cell studied by immunocytochemistry","volume":"13","author":"Jurco","year":"1982","journal-title":"Hum. Pathol."},{"key":"ref_8","first-page":"107","article-title":"von Willebrand factor and endothelial damage in essential hypertension","volume":"7","author":"Blann","year":"1993","journal-title":"J. Hum. Hypertens."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/S0950-821X(05)80112-4","article-title":"von Willebrand factor, endothelial cell damage and atherosclerosis","volume":"8","author":"Blann","year":"1994","journal-title":"Eur. J. Vasc. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0008-6363(97)00039-4","article-title":"von Willebrand factor: A marker of endothelial dysfunction in vascular disease","volume":"34","author":"Lip","year":"1997","journal-title":"Cardiovasc. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"19987","DOI":"10.1038\/s41598-021-99557-6","article-title":"Analysis focusing on plasma von Willebrand factor in pachychoroid neovasculopathy and age-related macular degeneration","volume":"11","author":"Hirai","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Hirai, H., Yamashita, M., Matsumoto, M., Nishiyama, T., Wada, D., Okabe, N., Mizusawa, Y., Jimura, H., Ueda, T., and Ogata, N. (2022). Alteration of plasma von Willebrand factor in the treatment of retinal vein occlusion with cystoid macular edema. PLoS ONE, 17.","DOI":"10.1101\/2022.02.18.22271170"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1159\/000542956","article-title":"Vasoproliferative retinal tumors: Manifestations, management, and Outcomes in a Case Series","volume":"16","author":"Pereira","year":"2025","journal-title":"Case Rep. Ophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1159\/000525939","article-title":"Noninvasive Imaging of a Vasoproliferative Retinal Tumor Treated with Cryopexy","volume":"13","author":"Tanimukai","year":"2022","journal-title":"Case Rep. Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.ophtha.2023.02.008","article-title":"Novel Manifestation of Retinal Hemangioblastomas Detected by OCT Angiography in von Hippel-Lindau Disease","volume":"130","author":"Takahashi","year":"2023","journal-title":"Ophthalmology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1146\/annurev.biochem.67.1.395","article-title":"Biochemistry and genetics of von Willebrand factor","volume":"67","author":"Sedler","year":"1998","journal-title":"Annu. Rev. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3212","DOI":"10.1182\/blood-2011-02-306597","article-title":"Unraveling the scissile bond: How ADAMTS13 recognizes and cleaves von Willebrand factor","volume":"118","author":"Crawley","year":"2011","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1055\/s-0038-1648251","article-title":"Targeting von Willebrand Factor in ischaemic stroke: Focus on clinical evidence","volume":"118","author":"Buchtele","year":"2018","journal-title":"Thromb. Haemost."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1182\/bloodadvances.2020003135","article-title":"Plasma levels of von Willebrand factor and future risk of incident venous thromboembolism","volume":"5","author":"Edvardsen","year":"2021","journal-title":"Blood Adv."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ayta\u015f, \u00c7., Cauduro, A., Falzone, C., Gianni, S., Tomba, A., and Cantile, C. (2025). Canine Hemangioblastoma: Case Series and Literature Review. Animals, 15.","DOI":"10.3390\/ani15203010"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1097\/ICB.0000000000001310","article-title":"Clinicopathological analysis of secondary retinal vasoproliferative tumor\/reactive retinal astrocytic tumor successfully treated by endoresection","volume":"18","author":"Hashimoto","year":"2024","journal-title":"Retin. Cases Brief Rep."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/12\/4440\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T07:15:19Z","timestamp":1781075719000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/12\/4440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,8]]},"references-count":21,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["jcm15124440"],"URL":"https:\/\/doi.org\/10.3390\/jcm15124440","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,8]]}}}